Compounds that elevate caMp levels in platelets are powerful inhibitors of activation. The exposure of platelets to prostacyclin and its analogues activate the ATP cyclase - cAMP dependent protein kinase pathway, and then several proteins, including a 22 kDa protein termed thrombolamban, are phosphorylated. We have recently discovered that thrombolamban is structurally related to low molecular weight GTP binding (G) proteins, which have regulatory functions in many types of cells. The goal of this project is to determine the role of thrombolamban in platelet inactivation. This is important because the mechanisms through which cAMP kinase substrates inhibit platelets, and small G protein regulate cell functions, are unknown. The proposed research is designed to detail an example of these mechanisms: the role of thrombolamban as a phospho- and G-protein in inhibiting platelets. My long term career plan is to conduct research in an academic setting, the primary goal of which is to elucidate molecular mechanisms that underlie platelet function. The principle tools for this investigation are those of biophysics and biochemistry, with emphasis being placed on acquiring methods as they are needed to accomplish specific tasks. Obtaining a Research Career Development Award would provide the support basis to conduct sustained investigation in an important aspect of platelet function: cAMP inhibition of the blood cell.